Scripps Research and GIS scientists map epigenome of human stem cells during development

LA JOLLA, CA - February 2, 2010 -- Scientists at The Scripps Research Institute and The Genome Institute of Singapore (GIS) led an international effort to build a map that shows in detail how the human genome is modified during embryonic development. This detailed mapping is a significant move towards the success of targeted differentiation of stem cells into specific organs, which is a crucial consideration for stem cell therapy.

The study was published in the genomics journal Genome Research on February 4, 2010.

"The cells in our bodies have the same DNA sequence," said Scripps Research Professor Jeanne Loring, who is a senior author of the paper with Chia-Lin Wei of the Genome Institute of Singapore and the National University of Singapore and Isidore Rigoutsos of IBM Thomas J. Watson Research Center. "Epigenetics is the process that determines what parts of the genome are active in different cell types, making a nerve cell, for example, different from a muscle cell."

Wei, who is senior group leader at the GIS, a biomedical research institute of the Agency for Science, Technology, and Research (A*STAR), said, "In this study, we mapped a major component of the epigenome, DNA methylation, for the entire sequence of human DNA, and went further by comparing three types of cells that represented three stages of human development: human embryonic stem cells, human embryonic stem cells that were differentiated into skin-like cells, and cells derived from skin. With these comprehensive DNA methylome maps, scientists now have a blueprint of key epigenetic signatures associated with differentiation."

DNA methylation causes specific subunits of DNA to be chemically modified, which controls which areas of the genome are active and which ones are dormant. DNA methylation is critical to the process in which embryonic cells change from "pluripotent stem cells," which have the ability to turn into hundreds of cell types, to "differentiated cells," distinct types of cells that make up different parts of the body, such as the skin, hair, nerves, etc.

In reviewing the data produced by the study--information on the methylation of three billion base pairs of DNA--the scientists were able to identify previously unknown patterns of DNA methylation. They identified cases where DNA methylation appeared to enhance, rather than repress, the activity of the surrounding DNA, and found evidence to suggest a role for DNA methylation in the regulation of mRNA splicing.

"We produced a very large amount of data," said Loring, "but it actually simplifies the picture. We identified patterns of many genes that are methylated or de-methylated during differentiation. This will allow us to better understand the exquisitely choreographed changes that cells undergo as they develop into different cell types."

Louise Laurent of Scripps Research and the University of California, San Diego, one of the first authors of the study, added, "The data are publicly available, and we are looking forward to learning what other scientists discover from using this information for their own studies on individual genes, embryonic development, and stem cells."

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Eleanor Wong, from the Genome Institute of Singapore, is also first author of the study, "Dynamic Changes in the Human Methylome During Differentiation." In addition to Laurent, Wong, Loring, Rigoutsos, and Wei, authors of the study are Guoliang Li, Thing Ong, and Hwee Meng Low of the Genome Institute of Singapore, Tien Huynh and Aristotelis Tsirigos of the IBM Thomas J. Watson Research Center, and Chin Ken Wing Kin Sung of the Genome Institute of Singapore and the National University of Singapore.

Funding for this work was provided by grants from the National Institutes of Health, the California Institute for Regenerative Medicine, A*STAR of Singapore, and The Esther B. O'Keeffe Foundation.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is located in Jupiter, Florida. See www.scripps.edu .

About the Genome Institute of Singapore

The Genome Institute of Singapore (GIS) is a member of the Agency for Science, Technology and Research (A*STAR). It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics, and biology towards the goal of individualized medicine. The key research areas at the GIS include systems biology, stem cell and developmental biology, cancer biology and pharmacology, human genetics, infectious diseases, genomic technologies, and computational and mathematical biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact. See www.gis.a-star.edu.sg.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences, and physical sciences and engineering research institutes, and seven consortia and centers, which are located in Biopolis and Fusionopolis, as well as their immediate vicinity. A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centers, and with other local and international partners. See www.a-star.edu.sg .

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